title: Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Protégé trial.
abstract: Protégé was a phase 3, randomized, double-blind, parallel, placebo-controlled 2-year study of three intravenous teplizumab dosing regimens, administered daily for 14 days at baseline and again after 26 weeks, in new-onset type 1 diabetes. We sought to determine efficacy and safety of teplizumab immunotherapy at 2 years and to identify characteristics associated with therapeutic response. Of 516 randomized patients, 513 were treated, and 462 completed 2 years of follow-up. Teplizumab (14-day full-dose) reduced the loss of C-peptide mean area under the curve (AUC), a prespecified secondary end point, at 2 years versus placebo. In analyses of prespecified and post hoc subsets at entry, U.S. residents, patients with C-peptide mean AUC >0.2 nmol/L, those randomized ≤6 weeks after diagnosis, HbA1c <7.5% (58 mmol/mol), insulin use <0.4 units/kg/day, and 8-17 years of age each had greater teplizumab-associated C-peptide preservation than their counterparts. Exogenous insulin needs tended to be reduced versus placebo. Antidrug antibodies developed in some patients, without apparent change in drug efficacy. No new safety or tolerability issues were observed during year 2. In summary, anti-CD3 therapy reduced C-peptide loss 2 years after diagnosis using a tolerable dose.
authors.affiliation: Pacific Northwest Diabetes Research Institute, Seattle, Washington.
authors.forename: William
authors.initials: W
authors.lastname: Hagopian
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ferry
authors.forename: Nicole
authors.initials: N
authors.lastname: Sherry
authors.forename: David
authors.initials: D
authors.lastname: Carlin
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonvini
authors.forename: Syd
authors.initials: S
authors.lastname: Johnson
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Stein
authors.forename: Scott
authors.initials: S
authors.lastname: Koenig
authors.forename: Anastasia G
authors.initials: AG
authors.lastname: Daifotis
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D019540:Area Under Curve; D002096:C-Peptide / Q000378:metabolism*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology / Q000628:therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007167:Immunotherapy; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D010919:Placebos
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; C502540:teplizumab